Conventional means for delivering biologically-active agents, including, but not limited to, pharmaceutical and therapeutic agents to animals often are severely limited by chemical and physical barriers imposed by the body. Oral delivery of many biologically-active agents would be the route of choice if not for the presence of chemical and physico-chemical barriers such as extreme and varying pH in the gastro-intestinal (GI) tract, exposure to powerful digestive enzymes, and impermeability of gastro-intestinal membranes to the active ingredient. Among the numerous pharmacological agents which are not suitable for oral administration are biologically-active peptides such as calcitonin and insulin. Examples of other compounds which are affected by the physico-chemical barriers are polysaccharides and mucopolysaccharides, including, but not limited to, heparin, heparinoids, antibiotics and other organic substrates. These agents are rapidly destroyed in the gastro-intestinal tract by acid hydrolysis, enzymes, or the like.
Prior methods for orally administering vulnerable pharmacological agents have relied on co-administration of adjuvants (e.g., resorcinols and non-ionic surfactants such as polyoxyethylene oleyl ether and n-hexadecyl polyethylene ether) to increase artificially the permeability of the intestinal walls; and on co-administration of enzymatic inhibitors (e.g., pancreatic trypsin inhibitor, diisopropylfluorophosphate (DFF) and trasylol) to avoid enzymatic degradation. Liposomes have also been described as drug delivery systems for insulin and heparin. See, for instance, U.S. Pat. No. 4,239,754; Patel et al. (1976) FEBS Letters Vol. 62, page 60; and Hashimoto et al. (1979) Endocrinol. Japan, Vol. 26, page 337. The broader use of the aforementioned methods, however, as drug delivery systems are precluded for reasons which include: (1) the use of toxic amounts of adjuvants or inhibitors; (2) the lack of suitable low MW cargoes; (3) the poor stability and inadequate shelf life of the systems; (4) difficulty in manufacturing; and (5) the failure of the systems to protect the active ingredient; and (6) the failure of the systems to promote absorption of the active agent.
More recently, microspheres of artificial polymers, or proteinoids, of mixed amino acids have been described for delivery of pharmaceuticals. For example, U.S. Pat. No. 4,925,673 describes such microspheres as well as methods for their preparation and use. The proteinoid microspheres of the '673 patent are useful for encapsulating a number of active agents.
There is a need in the art for a simple and inexpensive delivery system which is easily prepared and which can deliver a broad range of biologically-active agents.